Pharmacotherapy · 2022
Cumulative tenofovir diphosphate exposure in persons with HIV taking single- vs. multiple-tablet regimens.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Coyle Ryan P, Morrow Mary, MaWhinney Samantha, Coleman Stacey S, Zheng Jia-Hua, Ellison Lucas, Bushman Lane R, Kiser Jennifer J, Anderson Peter L, Castillo-Mancilla Jose R
Аннотация
BACKGROUND: We assessed cumulative antiretroviral exposure-using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS)-in persons with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) as single-tablet regimens (STR) or multiple-tablet regimens (MTR).
METHODS: Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed-effects models, adjusted for baseline characteristics, were used to compare TFV-DP in STR versus MTR. Models adjusted for ART regimen using either anchor drug class, pharmacokinetic booster status (unboosted [u/] or boosted [b/]), or a combined STR/MTR and booster categorical variable.
RESULTS: In the anchor class-adjusted model, STR had 19% (95% confidence interval [CI]: 3%-37%; p = 0.02) higher TFV-DP concentrations than MTR. However, in the booster-adjusted model, STR was not significantly higher than MTR (estimate 5%, 95% CI: -9% to 21%; p = 0.48), although PWH on b/ART had 35% (95% CI: 16%-58%; p = 0.0001) higher TFV-DP than u/ART. In the STR/MTR-boosted variable model, when compared to u/MTR, b/STR, b/MTR, and u/STR had 25% (95% CI: 7%-47%; p = 0.005), 37% (95% CI: 17%-59%; p < 0.0001), and 7% (95% CI: -7% to 24%; p = 0.34) higher TFV-DP, respectively. Compared with b/MTR, b/STR had 9% (95% CI: -31% to 10%; p = 0.37) lower TFV-DP. In a sensitivity analysis of PWH with HIV viral load <20 copies/ml at all visits, b/STR and b/MTR had 34% (95% CI: 16%-55%; p < 0.0001) and 12% (95% CI: -2% to 27%; p = 0.09) higher TFV-DP, respectively, compared with u/MTR, while u/STR had 4% (95% CI: -15% to 8%; p = 0.50) lower TFV-DP. Compared with b/MTR, b/STR had 17% (95% CI: 2%-30%; p = 0.03) higher TFV-DP.
CONCLUSIONS: Persons with HIV on b/TDF-based ART had higher TFV-DP than u/ART, regardless of STR or MTR use. No significant differences in TFV-DP between regimens of the same boosting status (i.e., b/STR vs. b/MTR; u/STR vs. u/MTR) were observed in the full cohort. Future research should examine the clinical utility of these findings in patient-tailored ART selection.
METHODS: Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed-effects models, adjusted for baseline characteristics, were used to compare TFV-DP in STR versus MTR. Models adjusted for ART regimen using either anchor drug class, pharmacokinetic booster status (unboosted [u/] or boosted [b/]), or a combined STR/MTR and booster categorical variable.
RESULTS: In the anchor class-adjusted model, STR had 19% (95% confidence interval [CI]: 3%-37%; p = 0.02) higher TFV-DP concentrations than MTR. However, in the booster-adjusted model, STR was not significantly higher than MTR (estimate 5%, 95% CI: -9% to 21%; p = 0.48), although PWH on b/ART had 35% (95% CI: 16%-58%; p = 0.0001) higher TFV-DP than u/ART. In the STR/MTR-boosted variable model, when compared to u/MTR, b/STR, b/MTR, and u/STR had 25% (95% CI: 7%-47%; p = 0.005), 37% (95% CI: 17%-59%; p < 0.0001), and 7% (95% CI: -7% to 24%; p = 0.34) higher TFV-DP, respectively. Compared with b/MTR, b/STR had 9% (95% CI: -31% to 10%; p = 0.37) lower TFV-DP. In a sensitivity analysis of PWH with HIV viral load <20 copies/ml at all visits, b/STR and b/MTR had 34% (95% CI: 16%-55%; p < 0.0001) and 12% (95% CI: -2% to 27%; p = 0.09) higher TFV-DP, respectively, compared with u/MTR, while u/STR had 4% (95% CI: -15% to 8%; p = 0.50) lower TFV-DP. Compared with b/MTR, b/STR had 17% (95% CI: 2%-30%; p = 0.03) higher TFV-DP.
CONCLUSIONS: Persons with HIV on b/TDF-based ART had higher TFV-DP than u/ART, regardless of STR or MTR use. No significant differences in TFV-DP between regimens of the same boosting status (i.e., b/STR vs. b/MTR; u/STR vs. u/MTR) were observed in the full cohort. Future research should examine the clinical utility of these findings in patient-tailored ART selection.